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04.03.2020 | Research Article

Body Mass Index and Age Effects on Brain 11β-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study

verfasst von: Jason Bini, Shivani Bhatt, Ansel T. Hillmer, Jean-Dominique Gallezot, Nabeel Nabulsi, Richard Pracitto, David Labaree, Michael Kapinos, Jim Ropchan, David Matuskey, Robert S. Sherwin, Ania M. Jastreboff, Richard E. Carson, Kelly Cosgrove, Yiyun Huang

Erschienen in: Molecular Imaging and Biology | Ausgabe 4/2020

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Abstract

Context

Cortisol, a glucocorticoid steroid stress hormone, is primarily responsible for stimulating gluconeogenesis in the liver and promoting adipocyte differentiation and maturation. Prolonged excess cortisol leads to visceral adiposity, insulin resistance, hyperglycemia, memory dysfunction, cognitive impairment, and more severe Alzheimer’s disease phenotypes. The intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to active cortisol; yet the amount of 11β-HSD1 in the brain has not been quantified directly in vivo.

Objective

We analyzed positron emission tomography (PET) scans with an 11β-HSD1 inhibitor radioligand in twenty-eight individuals (23 M/5F): 10 lean, 13 overweight, and 5 obese individuals. Each individual underwent PET imaging on the high-resolution research tomograph PET scanner after injection of ¹¹C-AS2471907 (n = 17) or ¹⁸F-AS2471907 (n = 11). Injected activity and mass doses were 246 ± 130 MBq and 0.036 ± 0.039 μg, respectively, for ¹¹C-AS2471907, and 92 ± 15 MBq and 0.001 ± 0.001 μg for ¹⁸F-AS2471907. Correlations of mean whole brain and regional distribution volume (V_T) with body mass index (BMI) and age were performed with a linear regression model.

Results

Significant correlations of whole brain mean V_T with BMI and age (V_T = 15.23–0.63 × BMI + 0.27 × Age, p = 0.001) were revealed. Age-adjusted mean whole brain V_T values were significantly lower in obese individuals. Post hoc region specific analyses revealed significantly reduced mean V_T values in the thalamus (lean vs. overweight and lean vs. obese individuals). Caudate, hypothalamus, parietal lobe, and putamen also showed lower V_T value in obese vs. lean individuals. A significant age-associated increase of 2.7 mL/cm³ per decade was seen in BMI-corrected mean whole brain V_T values.

Conclusions

In vivo PET imaging demonstrated, for the first time, correlation of higher BMI (obesity) with lower levels of the enzyme 11β-HSD1 in the brain and correlation of increased 11β-HSD1 levels in the brain with advancing age.

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Titel: Body Mass Index and Age Effects on Brain 11β-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study
verfasst von: Jason Bini
Shivani Bhatt
Ansel T. Hillmer
Jean-Dominique Gallezot
Nabeel Nabulsi
Richard Pracitto
David Labaree
Michael Kapinos
Jim Ropchan
David Matuskey
Robert S. Sherwin
Ania M. Jastreboff
Richard E. Carson
Kelly Cosgrove
Yiyun Huang
Publikationsdatum: 04.03.2020
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 4/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-020-01490-z

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Body Mass Index and Age Effects on Brain 11β-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study